Mechanistically, BACE1 cleavage may reduce gp130 signaling in two ways, a) by lowering the abundance of the full-length receptor gp130 and b) by generating sgp130, which can act as a decoy receptor as seen in our rescue experiments, but also demonstrated in vivo, where a Fc fusion protein of sgp130 is used to therapeutically lower IL6 trans signaling in mouse models of inflammatory diseases and cancer and in clinical trials for inflammatory bowel disease [88, 89]. Here, IL6ST is linked to inflammatory bowel disease.